Presentation is loading. Please wait.

Presentation is loading. Please wait.

Volume 21, Issue 4, Pages e4 (April 2017)

Similar presentations


Presentation on theme: "Volume 21, Issue 4, Pages e4 (April 2017)"— Presentation transcript:

1 Volume 21, Issue 4, Pages 530-537.e4 (April 2017)
Anaerobic Bacterial Fermentation Products Increase Tuberculosis Risk in Antiretroviral- Drug-Treated HIV Patients  Leopoldo N. Segal, Jose C. Clemente, Yonghua Li, Chunhai Ruan, Jane Cao, Mauricio Danckers, Alison Morris, Sarah Tapyrik, Benjamin G. Wu, Philip Diaz, Gregory Calligaro, Rodney Dawson, Richard N. van Zyl-Smit, Keertan Dheda, William N. Rom, Michael D. Weiden  Cell Host & Microbe  Volume 21, Issue 4, Pages e4 (April 2017) DOI: /j.chom Copyright © 2017 Elsevier Inc. Terms and Conditions

2 Cell Host & Microbe 2017 21, 530-537. e4DOI: (10. 1016/j. chom. 2017
Copyright © 2017 Elsevier Inc. Terms and Conditions

3 Figure 1 SCFAs Are Present in the Lungs of HIV-Infected Individuals on ART, Inhibiting IFN-γ and IL-17A Production after M. tuberculosis Antigen Stimulation (A) Acetate (open triangles), propionate (closed circles), and butyrate (open boxes) are present in BAL. Concentrations are corrected for BAL-induced dilution of epithelial lining fluid (ELF). Propionate is significantly elevated in HIV-infected subjects. Mann-Whitney U test. Error bars are median and interquartile range. (B) In HIV-infected individuals with paired samples, ELF SCFA concentration is higher than serum in all subjects, with a median ratio of 370. Error bars are median and interquartile range. (C) Addition of PPD to BAL cells demonstrates that induction of FoxP3 CD4+ cells significantly correlates with in vivo ELF acetate or propionate at the time of bronchoscopy. Spearman correlation. The dotted line is 95% confidence interval of linear regression. Cell Host & Microbe  , e4DOI: ( /j.chom ) Copyright © 2017 Elsevier Inc. Terms and Conditions

4 Figure 2 Butyrate Inhibits IFN-γ and IL-17A Production after M. tuberculosis Antigen Stimulation and Induces FoxP1 mRNA in CD4+ and CD8+ Lymphocytes (A) Compared with PPD, butyrate inhibits IFN-γ and IL-17A production by PPD stimulation. PBMCs of HIV-infected individuals on ART with latent TB were cultured in vitro without stimulation for 3 days (Unstim.), with PPD for 3 days (PPD), or with 2 mM butyrate added with PPD for 3 days (PPD + Butyrate). Paired t test of log-transformed data. (B) Addition of 2 mM butyrate inhibits IFN-γ and IL-17A expression in CD4+ and CD8+ lymphocytes stimulated with anti-CD3/CD28. Lymphocytes from six different individuals are shown. Paired t test of log-transformed data. (C) Addition of 2 mM butyrate increases FoxP1 mRNA expression in CD4+ and CD8+ lymphocytes. Paired t test of log-transformed FoxP/GAPDH. ns, not significant. Cell Host & Microbe  , e4DOI: ( /j.chom ) Copyright © 2017 Elsevier Inc. Terms and Conditions

5 Figure 3 Propionate-Detectable Individuals Have Increased Relative Abundance of Oral Anaerobic Bacteria in BAL (A) Rarefaction curve on taxonomic 16S rRNA gene annotation demonstrates no difference in α-diversity between the taxa in the microbiomes of 10 propionate-detectable and 29 propionate-undetectable individuals. Error bars are 95% confidence intervals. (B) A principal-component analysis based on UniFrac distance demonstrates a significant difference in the β-diversity between propionate-detectable and propionate-undetectable individuals (p value based on PERMANOVA). (C) LEfSe demonstrates enrichment of anaerobes such as Prevotella or Veillonella in the lung microbiome of propionate-detectable individuals. The histograms on top of the panel represent relative abundance of each taxa; error bars are mean with SD while the histograms below represent the linear discriminant analysis (LDA) value. The name of the enriched taxa is at the bottom of the panel. (D) There is a significant inverse correlation between BAL CD4+ lymphocytes and log10 transformed relative abundance of Prevotella or Veillonella in BAL. Spearman correlation. The dotted line is 95% confidence interval of linear regression. Cell Host & Microbe  , e4DOI: ( /j.chom ) Copyright © 2017 Elsevier Inc. Terms and Conditions


Download ppt "Volume 21, Issue 4, Pages e4 (April 2017)"

Similar presentations


Ads by Google